Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F : Characterization and relation to HLA haplotypes

The MOG locus, located on chromosomal bands 6p21.3-p22 and mapped about 100 kb telomeric to HLA-F, was isolated from cosmid ICRFcl09A2434 and shown to contain three microsatellites. These CA-repeat polymorphic markers were characterized in a sample of 173 healthy unrelated individuals and 84 DNAs from the HLA Workshop reference panel, by a method combining fluorescence labeling of PCR products and use of an automated DNA sequencer. For the three markers, frequencies of heterozygotes are well predicted from allele frequencies by the Hardy—Weinberg rule, which suggests that problems of allele nonamplification are unlikely. Typing of cell lines homozygous in the HLA region allowed unambiguous definition of 81 HLA-MOG haplotypes and showed that several HLA ancestral haplotypes extended to the MOG region. The high degree of polymorphism (59%, 51%, and 81% at the three loci, respectively, and 87% at the haplotype level) makes these new markers informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis, and for studies aimed at precisely delineating the site of crossover in chromosomes in which recombination occurred in the distal part of the HLA class I region.     

Use of live cold-adapted influenza A H1N1 and H3N2 virus vaccines in seropositive adults.

To investigate the immunogenicity and protective efficacy of cold-adapted influenza vaccine in individuals with underlying immunity to influenza A virus, we administered cold-adapted H1N1 and H3N2 vaccines to adults with prevaccination serum hemagglutination inhibition antibody titers of 1:16 or more and challenged them 1 month afterwards with homologous wild-type influenza A virus. Both cold-adapted vaccines were immunogenic in seropositive adults. In addition, individuals receiving cold-adapted vaccines had lower rates of virus shedding and illness following challenge with wild-type influenza virus than did unvaccinated seropositive volunteers.     

Biotinylation: a simple method for labelling complement component C8 with preservation of functional activity

Biotinylation of human C8 with the water-soluble biotin derivative biotinylamidohexanoic acid, N-hydroxysulfosuccinimide ester is an excellent method for labelling this terminal complement component with preservation of its functional activity. The biotinylated product can be detected both in native form and also following its incorporation into the terminal complement complexes. Detection assays include Western blotting, crossed immunoblotting, ELISA, and immunocytochemistry. Biotinylation is an attractive alternative method for labelling C8 and may be used for detecting and quantifying C8 and C5b-9 complexes in their soluble and membrane-bound forms.     

Ultrastructural and immunohistochemical characterization of autonomic neuropathy in genetically diabetic Chinese hamsters

Selected portions of the prevertebral and paravertebral sympathetic and vagal parasympathetic nervous systems have been examined in the genetically diabetic Chinese hamster, an experimental animal model of diabetic gastrointestinal disease. The prevertebral sympathetic superior mesenteric/celiac ganglia, which provide much of the sympathetic innervation of the alimentary tract, developed large numbers of markedly dilated axons, many of which had the ultrastructural features of neuroaxonal dystrophy. Dystrophic axons, many involving presynaptic axonal elements, were increased in frequency in the prevertebral superior mesenteric/celiac ganglia, but not in the paravertebral superior cervical sympathetic ganglia, of chronically diabetic hamsters in comparison with age-matched controls. Dystrophic axons contained substance P- and gastrin-releasing peptide (gastrin-releasing peptide/bombesin)-like staining but were not labeled by antisera directed against vasoactive intestinal peptide, dynorphin-B, somatostatin, leu- and met-enkephalin and neuropeptide tyrosine. Substance P and gastrin-releasing peptide/bombesin containing subpopulations of presynaptic elements in prevertebral sympathetic ganglia are thought to participate in local reflex control of bowel motility and lesions preferentially involving these elements may contribute to bowel dysfunction. Immunohistologic techniques failed to demonstrate dystrophic axons in the superior cervical ganglia. Although morphometric studies failed to show significant axon loss in the abdominal vagus of chronically diabetic Chinese hamsters, evidence of markedly diminished numbers of axons comprising each Schwann cell unit and regenerative collections of Schwann cell processes devoid of axons are consistent with the participation of parasympathetic elements in the pathogenesis of alimentary dysfunction in this model system. These results suggest that selective subpopulations of neuropeptide containing axons are vulnerable to the diabetic condition and that these abnormalities may lead to physiologic dysfunction.     

Sedative effects of antihistamines

The central effects of a newly developed, long-acting H1 antihistamine, loratadine (10 and 40 mg), were compared with those of a standard H1 antihistamine, diphenhydramine (50 mg three times a day) with measures of performance and daytime sleepiness (multiple sleep latency test). Sixteen healthy adults (six women and 10 men), 19 to 35 years of age, received each of the drugs and placebo for 2 days, separated by 5 days at home. Each day, the drug or placebo was administered at 8 A.M. and 12 and 4 P.M. Diphenhydramine was administered in three equal doses (50 mg), and loratadine was administered in a single dose followed by two placebo doses. Mean latency to sleep on tests done at 9 and 11 A.M. and 1, 3, and 5 P.M. was reduced significantly with diphenhydramine compared to placebo, whereas neither loratadine dose reduced sleep latency. Performance measured at 9:30 P.M. and 1:30 P.M. with a battery of tests, including reaction time, vigilance, digit symbol substitution, and symbol copying tasks demonstrated a significant reduction in symbols copied and digits substituted after diphenhydramine compared to both loratadine doses. These results demonstrate that loratadine (10 and 40 mg doses) did not have clinically significant central nervous system activity, whereas diphenhydramine increases sleepiness and disrupts performance efficiency.     

Left heart function in chronic obstructive lung disease

Summary In patients with varying degrees of chronic obstructive pulmonary disease (COPD), simultaneous measurements of central hemodynamics and left ventricular radionuclide ventriculograms at rest and during exercise were made. In 21 of these patients, satisfactory echocardiograms could be performed. In seven of the patients, arterial blood pressure at rest was increased. Decreased compliance of the left ventricle was thought to be present in patients with COPD and additional arterial hypertension. The left ventricular ejection fraction (LVEF) at rest was in the high normal range in all patients. During exercise, no further increase was observed. This pattern of LVEF response seems to be typical in patients with COPD. Because the highest values were observed in the more severe COPD and right ventricular hypertrophy, it is unlikely that an impairment of left ventricular function is caused by COPD. In five of 27 patients, an abnormal decrease of LVEF and regional hypokinesis occurred during exercise, thus suggesting additional coronary heart disease. The fact that at least 30% of the patients with COPD suffered from arterial hypertension and 20% of the patients exhibited unexpected ischemia detected by regional hypokinesis in RNV during exercise, but not in the ECG, may be of practical relevance. Coronary angiography was not indicated because most of these patients were over 65 and the factor limiting the working capacity was ventilatory impairment and not angina pectoris, in all patients. For this reason, a diagnostic uncertainty remains with regard to additional coronary heart disease in the older patients with advanced chronic obstructive pulmonary disease.Lung Function Parameters VC (1) inspiratory vital capacity - FEV1 (1) forced exspiratory volume in 1 sec - Raw (cmH20/l/s) airways resistance - RV/TLC (%) residual volume/total lung capacity - paO₂ (mm Hg) O₂ partial pressure Hemodynamic Parameters CI (1/min/sqm) cardiac index - SVI (ml/sqm) stroke volume index - PAP (mm Hg) pulmonary artery mean pressure - PwP (mm Hg) pulmonary capillary wedge pressure - RRs (mm Hg) systolic arterial pressure - RRd (mm Hg) diastolic arterial pressure (at the time of catheterization) - RR(WHO) (mm Hg) mean values measured at different days (at least 3 values). Parameters Derived from Combined Radionuclide Ventriculography and Central Hemodynamics LVEF (%) left ventricular ejection fraction - LVESVI (ml/sqm) left ventricular endsystolic volume index - P/V (mm Hg/ml/sqm) peak systolic pressure/endsystolic volume index - PFR (1/sec) peak filling rate: endsystolic volume/sec Echocardiographic Parameters RV d wth (mm) right ventricular enddiastolic wall thickness - LV d wth (mm) left ventricular enddiastolic wall thickness In honor to Prof. W.E. Adam's 60th birthday     

Right ventricular function in patients with chronic obstructive pulmonary disease

Summary Simultaneous right heart catheterization and radionuclide ventriculography were performed in 27 patients with a wide range of chronic obstructive pulmonary disease. Central hemodynamics and radionuclide studies were done at rest and during exercise. In the resting state the right ventricular ejection fraction (RVEF) was in the normal range (43.3±6%). During exercise a significant (p<0.001) decrease of RVEF to 38.8±6.7% occurred. The pumonary artery mean pressures were 19.9±3.8 at rest. During exercise a significant (p<0.001) increase to 41±9.8 mm Hg occurred. There was a linear relationship between pulmonary pressures and RVEF during exercise in patients with pulmonary artery pressures not exceeding 35 mm Hg. In patients with right ventricular end-diastolic wall thickness 6 mm a curvilinear relationship between these parameters could be observed with a flattening of the curve at higher pressures (>35 mm Hg) and lower ejection fractions (<35% RVEF). Radionuclide venticulography cannot substitute for right heart catheterization. Echocardiography is useful for interpretation of right ventricular ejection fractions in advanced chronic obstructive pulmonary disease.Abbreviations CI Cardiac index (l/min/m²) - CO Cardiac output (l/min) - COPD Chronic obstructive pulmonary disease - FEV₁ Forced expiratory volume in the first second (ml) - HR Heart rate (B/min) - PAd Pulmonary artery diastolic pressure (mm Hg) - PAP Pulmonary artery mean pressure (mm Hg) - PAs Pulmonary artery peak pressure (mm Hg) - PVR Pulmonary vascular resistance (dyn·s·cm^–5) - PwP Pulmonary capillary wedge pressure (mm Hg) - RAP Right arterial pressure (mm Hg) - Raw Airway resistance (cm H₂/l/s) - RNV Radionuclide ventriculogram - RV Residual volume (l) - RVEF Right ventricular ejection fraction (%) - RVEDVI Right ventricular enddiastolic volume index (ml/m²) - RVEDVI SVI RVEF (ml/m²) - RVESVI Right ventricular endsystolic index (m²/m²) - SVI Stroke volume index (ml/m²) - TLC Total lung capacity (l) - VC Vital capacity (l)     

Gastrin-releasing peptide, a mammalian analog of bombesin, is present in human neuroendocrine lung tumors.

Several reports have indicated that the amphibian peptide bombesin is present in oat-cell carcinoma of the human lung. The recent observation that gastrin-releasing peptide (GRP), a 27-amino acid peptide isolated from porcine intestine, may be the mammalian analog of bombesin led the authors to look for this peptide in human pulmonary tumors. Examination of 36 human lung tumors (8 carcinoids, 8 oat-cell carcinomas, and 20 non-oat-cell carcinomas) by immunohistochemistry and radioimmunoassay demonstrated the presence of high, although variable, levels of GRP in neuroendocrine tumors, and not in other histologic types. These findings indicate that bombesin immunoreactivity in human lung tumors should be attributed to GRP or GRP-like molecules and that GRP may be a useful marker of neuroendocrine differentiation.